Major Depressive Disorder or Bipolar Disorder? A Case of Mistaken Identity

In summary

• Delayed or inappropriate treatment of bipolar disorder (BD) leads to poorer outcomes for patients; therefore, early and accurate diagnosis is essential

• However, the initial presentation of BD can often mimic major depressive disorder (MDD) since major depressive episodes are a characteristic feature of both disorders, meaning misdiagnosis is common

• Subtle differences between BD and MDD do exist and have the potential to be identified in the clinic, based on close attention to multiple clinical features and a detailed patient history

 

Initial misdiagnosis of BD as MDD is common and may be due to under-reporting of mood elevation by patients, or simply because a manic episode is yet to have been experienced.^1–4 Mistaking these two conditions can lead to delayed or inappropriate treatment and poorer outcomes for patients.⁴ The initial presentation of BD can look much like MDD, since major depressive episodes are a characteristic feature of both disorders.⁴ There is also no difference in the duration of episodes between both illnesses.⁵ However, while many symptoms are common to both MDD and BD, closer analysis reveals that may be where the similarities end.

Differentiating BD from MDD: The clues in the presentation

While the crucial defining feature of BD is the occurrence of hypomanic or manic episodes, there may be some more subtle differences in depressive symptomatology. When comparing MDD and BD, somatic symptoms of depression and anxiety have been shown to be more common in MDD.⁴ In particular, insomnia, intellectual (cognitive), somatic (muscular), respiratory, gastrointestinal, genitourinary, and autonomic symptom scores have been shown to be significantly higher for patients with MDD than for patients with BD.⁴ Patients with BD tend to exhibit more severe tension/edginess and fearfulness than those with MDD, and are also more likely to demonstrate psychomotor-retarded melancholic and atypical depressive features.^4,6 Among the atypical symptoms more commonly reported by patients with BD are hypersomnia and leaden paralysis (feeling of heaviness in patients’ arms and legs).⁷

Patients with BD exhibit mood symptoms approximately 8 years earlier than those with MDD, and often have a greater number of prior depressive episodes at first presentation to a healthcare professional.^4,5 Patients with BD are also more likely to have had previous episodes of psychotic depression,⁶ and are much more likely to attempt suicide compared with patients with MDD.^8–10

Psychiatric comorbidities are common, with anxiety disorders occurring in 45% of patients with BD.¹¹ Rates of attention deficit hyperactivity disorder (ADHD) comorbidity in BD have been estimated as 10–20% of patients, whilst almost one-third of patients with BD are diagnosed with comorbid substance use disorder.^12,13 Additionally, when compared with the general population, patients with BD are seven times more likely to receive a lifetime diagnosis of obsessive-compulsive disorder or panic disorder.¹¹

Differentiating BD from MDD: The clues hiding beneath the surface

Neuroimaging studies reveal some key differences in brain pathology and function between the two disorders that suggest distinct pathophysiological processes. If a patient with BD is treated with antidepressant therapy that is better indicated for patients with MDD, this can give rise to manic or mixed states, or cycle acceleration.^4,14 Patients with BD demonstrate more widespread white matter abnormalities and greater reductions in gray matter volume, while also exhibiting different aberrant functional connectivity in the neural circuitries responsible for emotion regulation, attentional control, and reward processing, compared with patients with MDD.⁵

Another differential that holds promise is genetics. The identification of disorder-specific biomarkers in individuals with MDD or BD may provide greater clarity on the differentiation between the two disorders. This could be made possible by detecting RNA-editing signatures in genes involved in different pathways relevant to BD and MDD and using these to confirm a diagnosis. This would provide a better understanding of the molecular pathophysiology of both disorders and may pave the way for the development of a diagnostic assay for clinical application.¹⁵

So, is it BD or not?

In summary, there is rarely one defining feature of BD; therefore, it is important to differentiate BD from MDD based on close attention to multiple clinical features and a detailed patient history. Features that may suggest BD include:

• Atypical symptoms and signs, including hyperphagia, hypersomnia, anxiety, and agitation^16,17

• History of psychosis^16,17

• Age <25 years at onset^16,17

• Comorbid anxiety disorder, substance use disorder, and/or ADHD¹⁸

• A history of poor response to antidepressants¹⁹

Further reading

• Shen H, et al. Analysis of Misdiagnosis of Bipolar Disorder in An Outpatient Setting. Shanghai Arch Psychiatry 2018;30:93–101.
  What are the reasons for misdiagnosis of BD in the outpatient setting?

• Perlis RH, et al. Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry 2006;163:225–231.
  How can you recognize the subtle differences in presentation between BD and MDD?

• Fung G, et al. Distinguishing bipolar and major depressive disorders by brain structural morphometry: a pilot study. BMC Psychiatry 2015;15:298.
  Are there distinct differences in neuroanatomical features in the brains of patients with BD and MDD?

ADHD, attention deficit hyperactivity disorder; BD, bipolar disorder; MDD, major depressive disorder.

Major Depressive Disorder or Bipolar Disorder? Connecting Psychiatry. Published May 2023.

SC-US-75169

SC-CRP-13471

April 2023